ABSTRACT

The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants’ clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.

METHODS

We performed a search on March 12, 2020, at the clinicaltrials. gov database, with the descriptor [coronavirus] in the simple search field “conditions or disease” search, without restrictions on languages, disease conditions, results, or locations. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the study period; describe the patient’s clinical conditions; and interventions utilize medicines already studied or approved for any other disease in patients with COVID-19. ClinicalTrials.gov is a resource from the US National Library of Medicine, and it contains clinical studies conducted by 209 countries.

Recombinant human interferon α2β is described to have inhibitory effects on MERS-CoV and SARS-CoV (4848. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2020 Mar 12 – Identifier NCT04293887, Efficacy and safety of IFN-α2β in the treatment of novel coronavirus patients. Available from: https://clinicaltrials.gov/ct2/show/NCT04293887?term=NCT04293887&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT0... ), and the purpose of the clinical trials found for this paper is to evaluate the efficacy and safety of recombinant human interferon α2β in treating patients with new coronavirus infection (4949. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2020 Mar 12 – Identifier NCT04273581, The efficacy and safety of thalidomide combined with low-dose hormones in the treatment of severe Covid-19. Available from: https://clinicaltrials.gov/ct2/show/NCT04273581?term=NCT04273581&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT0... ).

Thalidomide will be used in two trials against COVID-19 (4949. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2020 Mar 12 – Identifier NCT04273581, The efficacy and safety of thalidomide combined with low-dose hormones in the treatment of severe Covid-19. Available from: https://clinicaltrials.gov/ct2/show/NCT04273581?term=NCT04273581&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT0... , 5050. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2020 Mar 12 – Identifier NCT04273529, The efficacy and safety of thalidomide in the adjuvant treatment of moderate new coronavirus (Covid-19) pneumonia. Available from: https://clinicaltrials.gov/ct2/show/NCT04273529?term=NCT04273529&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT0... ). Thalidomide has an anti-inflammatory action due to its ability to speed up the degradation of messenger RNA in blood cells and thus reduce tumor necrosis factor-α (TNFα). Furthermore, thalidomide can increase the secretion of interleukins, such as IL-12, and activate natural killer cells (5151. Newfield C. New Medical Indications for Thalidomide and its Derivatives New Medical Indications for Thalidomide and its Derivatives. The Science Journal of the Lander College of Arts and Sciences. 2018;12(1).).

In conclusion, the WHO declared an epidemic of pneumonia caused by the SARS-CoV-2 in 2020. In this review, we found 24 clinical trials that have already started with the repositioning of more than 20 medicines for COVID-19 treatment, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, oseltamivir, thalidomide, methylprednisolone, bevacizumab, and TCM. The Hydroxychloroquine-azithromycin combination was the first drug repurposed with excellent results in clinical trials against SARS-CoV-2, but further, more extended studies, with a higher number of patients, are needed to confirm these results. Besides its limitations, repositioning clinical trials are still an attractive strategy: they may facilitate the discovery of new classes of medicines; they may reduce the costs and time to reach the market; there is an existing pharmaceutical supply chain for formulation and distribution; and there is the possibility of combinations with other drugs in treatments that are more effective than monotherapy. Most of the studies found in this article are scheduled to end in 2020, and we hope these repositioning trials may help to find solutions for COVID-19 treatment by this year.

Disclaimer.

Authors hold sole responsibility for the views expressed in the manuscript, which may not necessarily reflect the opinion or policy of the RPSP/PAJPH and/or PAHO.

Newfield C. New Medical Indications for Thalidomide and its Derivatives New Medical Indications for Thalidomide and its Derivatives. The Science Journal of the Lander College of Arts and Sciences. 2018;12(1).